Cell-cycle-dependent dynamics of nuclear pores: pore-free islands and lamins

Kazuhiro Maeshima,Kazuhide Yahata,Naoko Imamoto,Reiko Nakatomi,Fumio Imamoto,Taro Tachibana,Yoko Sasaki,Tsutomu Hashikawa

doi:10.1242/jcs.03207

Kazuhiro Maeshima, Kazuhide Yahata + Show 6 more

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Nuclear pores are sophisticated gateways on the nuclear envelope that control macromolecular transport between the cytoplasm and nucleoplasm. So far the structural and functional aspects of nuclear pores have been extensively studied, but their distribution and density, which might reflect nuclear organization and function, remain unknown. Here, we report the cell-cycle-dependent dynamics of nuclear pores. Large distinct subdomains lacking nuclear pores are present on the nuclear surface of HeLaS3 cells in early cell-cycle stages. Such ;pore-free islands' gradually become dispersed in G1-S phase. Surprisingly, the islands are enriched with inner nuclear membrane proteins lamin A/C and emerin, but exclude lamin B. Lamin-A/C-enriched pore-free islands were also observed in human normal diploid fibroblasts and several cell lines, showing the generality of this phenomenon. Knockdown and ectopic expression analyses demonstrated that lamin A/C, but not emerin, plays an essential structural and regulatory role in the nuclear pore distribution and the formation of pore-free islands. These data thus provide strong evidence that the dynamics of nuclear pores are regulated by the reorganization of inner nuclear structures.

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The eukaryotic nucleus is a complex and sophisticated organelle that contains genomic chromatin, and supports many essential cellular activities, including DNA replication, RNA transcription and processing, and ribosome assembly. Such nuclear functions are largely dependent upon the structural organization of the nucleus and the formation of a membranous structure, the nuclear envelope (NE), which separates the nucleoplasm from the cytoplasm (Gerace and Burke, 1988)
That emerin and lamin A/C, which are linked to a variety of human genetic disorders including Emery-Dreifuss muscular dystrophy, are highly enriched in the pore-free islands (Fig. 3A, first and third rows and supplementary material Fig. S1B)
The lamin-A enrichment induced the clustering of nuclear pores. These results demonstrate that an ectopic expression of lamin A effectively facilitates the formation of pore-free islands on the nuclear envelope

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Introduction

The eukaryotic nucleus is a complex and sophisticated organelle that contains genomic chromatin, and supports many essential cellular activities, including DNA replication, RNA transcription and processing, and ribosome assembly Such nuclear functions are largely dependent upon the structural organization of the nucleus and the formation of a membranous structure, the nuclear envelope (NE), which separates the nucleoplasm from the cytoplasm (Gerace and Burke, 1988). Mutations in the lamin A/C gene, as well as in several genes that encode inner nuclear membrane proteins that bind to the lamina, have been shown to cause a variety of human genetic disorders: the so-called ‘laminopathies’, including Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford progeria syndrome (HGPS) (Burke and Stewart, 2002; Hutchison and Worman, 2004; Mounkes et al, 2003; Wilson, 2000)

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